US Pharm. 2015;40(6):36-38.

The cornea has a first-time transplantation success rate of about 90%; however, second corneal transplants suffer from a rejection rate triple that of first transplants.

“Understanding why these rejections occur is important to further improving the ways in which corneal transplants are performed,” said the study’s senior author Jerry Niederkorn, PhD, professor and vice chair of research in the department of ophthalmology and professor of microbiology at UT Southwestern Medical Center, Dallas. “In the future, ophthalmologists may be able to implement processes, and eventually prescribe medications, that can lower the rates of rejection.” The study appears in the American Journal of Transplantation.

Each year, more than 40,000 transplants are performed to replace the cornea. Most corneal transplants are done to correct severe visual impairments caused by keratoconus, a condition wherein the dome-shaped cornea thins and becomes cone-shaped.

The high success rate of initial corneal transplants is attributed to a process called immune privilege, which allows transplants to be successfully performed without matching the donor tissue to that of the recipient, as is required for organ transplants. Even though immune privilege is responsible for the initial high success rate, it can fail, leading to the rejection of corneal transplants in approximately 10% of patients. In patients requiring a second transplant, the incidence of immune rejection rises to almost 70%.

Researchers studying mouse models discovered that after the first corneal transplant is accepted, T regulatory cells prevent other types of immune cells from attacking and rejecting the transplant.

But severing corneal nerves, which occurs during the first transplantation, releases high levels of the neuropeptide Substance P. The resulting high Substance P levels disable the T regulatory cells needed for acceptance of subsequent corneal transplants. Researchers found that the high Substance P levels can be blocked with drugs to restore the eye’s immune privilege and promote the acceptance of second transplants.